In recent years, inactivated vaccines and attenuated vaccines were developed for emerging or reemerging infections, and high prophylaxis effects have been obtained. However, the development of vaccine against infections is far behind in Japan. For eradication of particular infection and dealing with pandemic in the developing countries, the development of a vaccine permitting large-scale production and long-term preservation, and having high safety and strong titer has been desired. Among others, a DNA vaccine permitting large-scale production at a low cost is expected to prove effective; however, the development thereof is not successful from the aspects of safety and titer. In addition, the development of a preparation suitable for intravenous injection, subcutaneous or intradermal injection that activates body immunity, and a preparation suitable for oral, inhaled or nasal administration that activates mucosal immunity is necessary.
Moreover, it has been reported that a vaccine against human papilloma virus has been approved as a cervical cancer vaccine and shows a high effect. However, a vaccine therapy of cancer antigen has not been established as yet in the world. While vaccines using various antigens and DNAs have been reported, a sufficient immunity induction effect was not obtained and clinical application has not been commenced. Particularly, DNA vaccine is expected to selectively activate cellular immunity relating to cancer, and potentiate the anticancer immunity. While DNA vaccine is drawing attention since it permits large-scale production at a low cost, there is no successful case in terms of safety and titer.
Since DNA pharmaceutical products show different pharmacological actions by changing the combination of bases and permit large-scale production at a low cost, they are expected to prove effective as pharmaceutical products. Heretofore, various nanostructures have been developed as a vector for gene delivery, and their organ specificity and cell specificity have been reported. However, since safety and efficiency are low, they have not been put to clinical use. Since many of them use synthetic materials, safety has not been established and the medical economy is large. The development of an organ specific vector having high safety and broad utility has been desired.
There are some methods to make a vector organ specific, one of which is a method using a particular molecule that easily accumulates in a target organ, and the other is a method using a molecule having a specific binding ability, which is an antibody, an aptamer and the like.
As the former method, the present inventors have succeeded in the construction of a novel targeting system having selectivity to the spleen and the lung, by applying the technique of a drug delivery complex (patent document 1) and conveniently adding a biodegradable lipid. To be specific, the safety of nanoparticles was enhanced by a simple addition of phosphatidylserine (negative charge) to a cationic nucleus encapsulating a DNA, and gene expression selective only to the spleen could be realized by intravenous injection to a mouse. The spleen contains an abundance of immunocytes, and a spleen-selective gene expression leads to the development of DNA vaccine. Furthermore, the addition of N-lauroylsarcosine (negative charge) instead of phosphatidylserine resulted in the gene expression only in the lung after its intravenous injection to a mouse and enhanced the safety of nanoparticles (non-patent document 1).